A major post-translational modification is glycosylation. Glycosylation is the attachment of monosaccharides and oligosaccharides to a protein backbone via a glycosidic linkage. It is estimated over 80% of all plasma proteins are glycosylated.
There are two main types of glycosylation:
- N-linked - where the sugar units are attached via the amide nitrogen of an asparagine residue; and
- O-linked - where the sugar units are attached via the hydroxyl group of serine, threonine, hydroxylysine or hydroxyproline residues.
Other glycosidic linkages include S-linkage to cysteine and C-linkage to tryptophan.
A glycoprotein showing post-translational modifications
The oligosaccharide chains are shown in spacefill (balls) and the polypeptide is in ORANGE (ribbon). The Asn residues to which the oligosaccharides are attached are shown in BLUE. The oligosaccharide sequence starts with two N-acetylglucosamine residues (YELLOW) and has several other monosaccharide residues (RED) attached.
The addition of specific sugar residues to individual amino acids in a polypeptide is not a random event. It is generally believed that each polypeptide glycosyltransferase recognises specific amino acid sequence motifs. N-linked glycosylation occurs at asparagines in the consensus sequence -Asn-Xaa-Ser/Thr/Cys where Xaa is not Proline. Similarly, C-glycosylation occurs at tryptophan residues in the motifs -Trp-Xaa-Xaa-Trp or Trp-Ser/Thr-Xaa-Cys. There is no known motif for O-glycosylation, but it is known O-glycosylation is more probable in sequences with a high proportion of serine, threonine and proline residues.
If you want to find out more about the glycosylation characteristics of our proteins,click here to view summary data.
The presence of a potential glycosylation amino acid sequence motif does not guarantee the site is glycosylated. Furthermore, each glycosylated site may be fully or partially glycosylated, and one site may have many different glycan structures.
This protein glycosylation complexity results because the glycosylation process is not under direct genetic control. Instead glycosylation is a finely controlled process that is dependent upon the availability and activity of the various glycosyltransferases, monosaccharides and precursors.
More indirectly, levels of various hormones, such as thyrotropin and retinol (vitamin A), also regulate glycosylation through a variety of cell type dependent effects. The result is that the same protein derived at different times of development or from different tissues can possess different glycan chains.